The primary goal of this project is to address systematically practical questions of clinical importance in order to facilitate the transition of penicillin skin testing from investigational status to widespread judicious use by practicing physicians. In addition, more fundamental questions with broader implications for the general problem of penicillin allergy are being explored. The project involves continuation of a longitudinal clincial study of multiple aspects of penicillin allergy in a sexually transmitted disease (STD) clinic population. A principal objective is to define more precisely clinical indications for, as well as limitations of, penicillin skin tests. A prospective, randomized, controlled clinical trial of the routine use of penicillin skin testing in patient without prior adverse reactions to penicillin is underway, and will be continued to the point where statistically valid estimates of the costs and benefits can be established. The expected benefits from such prophylactic skin testing are a reduction of acute morbidity and mortality from penicillin allergic reactions. Current clinical research protocols implemented in the STD clinic are addressing the following additional questions: (a) determination of optimal skin testing reagents, particularly with regard to the composition of the "minor determinant" penicillin antigenic mixture; (b) further definition of the risks and benefits of treating history positive but currently skin test negative patients, specially with regard to results obtained with the use of intramuscular penicillins; (c) evaluation of the relationship of IgE-mediated penicillin reactions to the common non-urticarial exanthems, particularly with regard to the utility of skin testing, and the risk of retreatment; (d) determination of the predictive value pre-treatment serological profiles of penicilloyl IgG and IgE antibodies, for post-treatment reactions; (e) documentation of the natural history of IgE-mediated penicillin allergies by determining the rate of disappearance of positive penicillin skin tests and penicilloyl serum antibodies; and (f) correlation of the results of penicilloyl RAST analysis of serum with direct skin tests using penicilloyl polylysine.